DHEA Hormone Replacement

by Ben Best

DHEA Changes with Aging

DeHydroEpiAndrosterone (DHEA) and its sulfate (DHEAS)
are the most abundant steroid hormones in the human bloodstream. Blood levels are highest
in the developing foetus, drop sharply after birth, begin climbing again at age 6−8
(a time of rapid growth) to a peak at age 25−30 and then decline to about 10%
of the peak level by age 80. Adult blood levels of DHEAS are 100−500 times higher
than testosterone and 1,000−10,000 times higher than
estradiol [THE JOURNAL OF ENDOCRINOLOGY; Labrie,F; 187(2):169-196 (2005)].

DHEA circulates in the bloodstream mainly as the sulfated form, DHEAS.
The half-life of DHEAS is 7−10 hours, whereas the half-life of DHEA is only
15−30 minutes. DHEAS is coverted to DHEA and then to sex hormones in body
tissues. No change in DHEAS serum levels is seen beyond the age of 90, and
men over 90 with the highest serum DHEAS levels show the best functional
status [THE JOURNAL OF CLINICAL ENDOCRINOLOGY &AMP; METABOLISM; Ravaglia,G; 81(3):1173-1178 (1996)].

With the exception of high-affinity G-protein DHEA receptors on endothelial cells, there
are no receptors for DHEA, which some have interpreted as meaning that it serves mainly as
a precursor to other hormones. A sense of futility (or acceptance) concerning aging-associated functional
decline, the diversity & vaguely-understood nature of DHEA actions and the fact that DHEA is a
natural hormone that cannot be patented have all contributed to the relative lack of research that has been
done on the value of DHEA hormone replacement.

About half of the body's DHEA is produced in the adrenal cortex — with the rest coming from gonads,
fat tissue and (notably) the brain. The steroid synthesis pathway is:

cholesterol -> pregnenolone -> DHEA
-> testosterone -> estrogen

DHEA-S to DHEA

Humans have considerably higher levels of DHEA than any other species.
Even non-human primates produce not much more than 10% of the DHEA
that humans produce. Sex hormones
are produced almost exclusively by the ovary & testes of most mammals,
whereas for humans (and to a lesser extent some other primates) about half
of the sex hormones come from the gonads and about half is synthesized on
an as-needed basis from DHEA in peripheral tissues (breast, prostate,
brain, muscle, liver, etc.) For post-menopausal women, DHEA is the only
source of sex hormones in peripheral tissues.

In one study 82% of women compared to 67% of men have reported improved "well being" (better sleep,
more energy, better able to handle stress) when taking
DHEA [BMJ; Weksler,ME;
312(7035):859-860(1996)]. A 50 mg DHEA per day four-month double-blind study of women having low
DHEA due to adrenal gland insufficiency showed significantly reduced anxiety & depression leading
to reduced exhaustion. Increased sexuality was associated with androgenic effects. The improvements
were seen after four months, but not after one month — indicating the value of the longer-term
study [NEW ENGLAND JOURNAL OF MEDICINE; Arlt,W; 341(14):1013-1020 (1999)].

The aforementioned NEW ENGLAND JOURNAL OF MEDICINE study by Nair was greeted by many as proof
positive that DHEA supplementation is of no value. Double-blinded and placebo-controlled, the
study compared roughly 30 each of elderly men & women on DHEA against the same
number of controls (about 30 men and 30 women) over a 2 year period. No
adverse effects were found and no benefit was seen for bone mineral density, body muscle-fat
composition, physical performance, insulin resistance or quality of life. The study did
acknowledge some bone mineral density increase, but this result was dismissed as inconsequential.
Another placebo-controlled, double-blind study of almost the same size and study population lasting
6 months using 50 mg/day of DHEA on elderly men & women showed significant
decreases in visceral & subcutaneous fat as well as increases in insuling sensitivity and
IGF−1 levels — suggesting that DHEA may be of use
against the metabolic
syndrome [JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION; Villareal,DT; 292(18):2243-2248 (2004)].

The NEW ENGLAND JOURNAL OF MEDICINE study by Nair that dismissed DHEA supplementation as
being without value made no assessment of endothelial function, effects of cortisol on the
hippocampus, of immune function, of skin status and of a number of other parameters.